Current Concepts and Controversies in Innate Immunity of Cystic Fibrosis Lung Disease

Abstract

Cystic fibrosis (CF) lung disease is characterized by chronic infection and inflammation. The inflammatory response in CF is dominated by the activation of the innate immune system. Bacteria and fungi represent the key pathogens chronically colonizing the CF airways. In response, innate immune pattern recognition receptors, expressed by airway epithelial and myeloid cells, sense the microbial threat and release chemoattractants to recruit large numbers of neutrophils into CF airways. However, neutrophils fail to efficiently clear the invading pathogens, but instead release harmful proteases and oxidants and finally cause tissue injury. Here, we summarize and discuss current concepts and controversies in the field of innate immunity in CF lung disease, facing the ongoing questions of whether inflammation is good or bad in CF and how innate immune mechanisms could be harnessed therapeutically.

Fig. 1

Innate immune activation in CF airways. Due to continuous production of cytokines and chemokines, especially IL-8, neutrophils are recruited into the CF airways. Bacterial and fungal PAMPs and host-derived DAMPs further activate downstream signaling pathways through the activation of PRRs, and lead to enhanced cytokine and chemokine production. Infiltrated neutrophils release proteases and oxidants, resulting in perpetuated inflammation and tissue injury.